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Historic HeLa Cells Sequenced

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Researchers at the Heidelberg-based European Molecular Biology Laboratory report they have successfully sequenced the genome of a HeLa cell line. According to the investigators, their results provide a high-resolution genomic reference that reveals the striking differences between the HeLa genome and that of normal human cells. The study, published in G3: Genes, Genomes and Genetics online, could improve the way HeLa cells are used to model human biology, they add.

HeLa cells are the world's most commonly used human cell lines, and have served as a standard for understanding many fundamental biological processes. The scientists' analysis of the HeLa genome revealed widespread abnormalities in both the number and structure of chromosomes, as well as factors commonly associated with cancer cells like losing healthy copies of genes. In particular, the researchers found that countless regions of the chromosomes in each cell were arranged in the wrong order and had extra or fewer copies of genes. This is a telltale sign of chromosome shattering, a recently discovered phenomenon associated with 2–3% of all cancers.

Knowledge of the genetic landscape of these cells can inform the design of future studies using HeLa cells, and strengthen the biological conclusions that can be made from them, explain two of the key team members.

“The results provide the first detailed sequence of a HeLa genome,” said Jonathan Landry, Ph.D., and Paul Pyl from EMBL. “It demonstrates how genetically complex HeLa is compared to normal human tissue. Yet, possibly because of this complexity, no one had systematically sequenced the genome, until now.”

“Our study underscores the importance of accounting for the abnormal characteristics of HeLa cells in experimental design and analysis, and has the potential to refine the use of HeLa cells as a model of human biology,” added Lars Steinmetz, Ph.D., from EMBL, who led the project.

For decades HeLa cells have provided effective and usable biological models for researching human biology and disease. They are widely regarded as the industry standard tool for studying human biology. Studies using them have led to two Nobel prizes and a host of advancements in many areas, including cancer, HIV/AIDS, and the development of the polio vaccine.

The HeLa genome had never been sequenced before, and modern molecular genetic studies using HeLa cells are typically designed and analyzed using the Human Genome Project reference. This, however, misrepresents the sequence chaos that characterizes HeLa cells, since they were derived from a cervical tumor and have since been adapting in laboratories for decades, pointed out Dr. Steinmetz.

He explains that the study provides a high-resolution genetic picture of a key research tool for human biology. It highlights the extensive differences that cell lines can have from the human reference, indicating that such characterization is important for all research involving cell lines and could improve the insights they deliver into human biology.

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